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Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats

SYSNO ASEP	0555872
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats
Author(s)	Štefková-Mazochová, K. (CZ) Danda, H. (CZ) Dehaen, W. (CZ) Jurásek, B. (CZ) Šíchová, K. (CZ) Pinterová-Leca, N. (CZ) Mazoch, V. (CZ) Hrčka Krausová, Barbora (FGU-C)_{ORCID, RID} Kysilov, Bohdan (FGU-C)_{ORCID, SAI} Smejkalová, Tereza (FGU-C)_{RID, ORCID} Vyklický ml., Ladislav (FGU-C)_{RID, ORCID, SAI} Kohout, M. (CZ) Hájková, K. (CZ) Svozil, Daniel (UMG-J) Horsley, R. R. (CZ) Kuchař, M. (CZ) Páleníček, T. (CZ)
Source Title	British Journal of Pharmacology. - : Wiley - ISSN 0007-1188 Roč. 179, č. 1 (2022), s. 65-83
Number of pages	19 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	deschloroketamine ; enantiomers ; locomotion ; NMDA receptor ; pharmacokinetics ; pharmacokinetics
OECD category	Pharmacology and pharmacy
R&D Projects	GA20-17945S GA ČR - Czech Science Foundation (CSF)
	EF16_025/0007444 GA MZd - Ministry of Health (MZ)
	LM2018130 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Research Infrastructure	CZ-OPENSCREEN III - 90130 - Ústav molekulární genetiky AV ČR, v. v. i.
Method of publishing	Open access
Institutional support	FGU-C - RVO:67985823 ; UMG-J - RVO:68378050
UT WOS	000713032600001
EID SCOPUS	85118308442
DOI	10.1111/bph.15680
Annotation	Background and purpose: Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to date. Experimental approach: Pharmacokinetics, acute effects, and addictive potential in a series of behavioural tests in Wistar rats were performed following subcutaneous (s.c.) administration of DCK (5, 10, and 30 mg center dot kg(-1)) and its enantiomers S-DCK (10 mg center dot kg(-1)) and R-DCK (10 mg center dot kg(-1)). Additionally, activity at human N-methyl-d-aspartate (NMDA) receptors was also evaluated. Key results: DCK rapidly crossed the blood brain barrier, with maximum brain levels achieved at 30 min and remaining high at 2 h after administration. Its antagonist activity at NMDA receptors is comparable to that of ketamine with S-DCK being more potent. DCK had stimulatory effects on locomotion, induced place preference, and robustly disrupted PPI. Locomotor stimulant effects tended to disappear more quickly than disruptive effects on PPI. S-DCK had more pronounced stimulatory properties than its R-enantiomer. However, the potency in disrupting PPI was comparable in both enantiomers. Conclusion and implications: DCK showed similar behavioural and addictive profiles and pharmacodynamics to ketamine, with S-DCK being in general more active. It has a slightly slower pharmacokinetic profile than ketamine, which is consistent with its reported longer duration of action. These findings have implications and significance for understanding the risks associated with illicit use of DCK.
Workplace	Institute of Physiology
Contact	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Year of Publishing	2023
Electronic address	https://doi.org/10.1111/bph.15680

Number of the records: 1